目的：应用高分辨率光标测技术，观察INa‐L 、IKr对左、右心室间异质性及频率依赖性的影响。方法构建兔离体心脏模型（12只），将电压敏感性染料通过Langendorff方法灌注兔离体心脏，使用波长为532 nm的LED光源，分別记录心脏左、右心室动作电位时程（APD80和 APD50）；分别使用多菲利特（30 nmol／L ）、多菲利特＋ ATX‐Ⅱ（1 nmol／L）、多菲利特＋ ATX‐Ⅱ＋美西律（10μmol／L）进行灌注，加药前为自身对照，每组分别给予刺激周长（BCL）为2000、1000、500、300 m s的刺激，观察药物干预前后左心室或右心室A PD的变化。结果①在不同刺激条件下，对照组右心室的APD80、APD50均长于左心室，呈反向频率依赖性；②加入多菲利特后，BCL＝1000 ms时，左、右心室的A PD80、A PD50分别较对照组相应心室明显延长，但两心室的ΔA PD80和ΔA PD50相比差异有统计学意义（ P＞0．05）；随频率的减慢，两心室的ΔAPD80较对照组增加明显。③加入 ATX‐Ⅱ后，BCL ＝1000 ms时，左、右心室的 APD80、A PD50较单用多菲利特及对照组显著增加，两心室的ΔA PD80和ΔA PD50相比差异均有统计学意义（ P＜0．05），且左心室的ΔA PD80和ΔA PD50大于右心室。随刺激频率的减慢，两心室的ΔA PD80较对照组显著增加。④加入美西律后， BCL＝1000 ms时，左、右心室的APD80、APD50较使用前明显缩短，两心室的ΔAPD80和ΔAPD50与对照组相比差异有统计学意义（P＜0．05），两心室的ΔAPD80与ATX‐Ⅱ组相比差异有统计学意义（P＜0．05），而ΔAPD50与ATX‐Ⅱ组相比差异无统计学意义（P＞0．05）。随频率的减慢，两心室ΔAPD80增加的幅度减小。结论①多菲利特阻断IKr未能增大心室间的异质性，左、右心室表现出反向频率依赖性。②在阻断IKr的基础上使用INa‐L开放剂ATX‐Ⅱ，增加了左、右室间的异质性，并加强IKr的反向频率依赖性；美西律阻断INa‐L减小心室间的异质性，并减轻其反向频率依赖性。%ABSTRACT:Objective To observe the effects of late Na current (INa‐L ) and rapidly activating delayed rectifier K current (IKr ) on ventricular heterogeneity and frequency dependency by using high resolution voltage sensitive optical mapping technology .Methods The model of 12 isolated hearts was constructed in rabbits . Voltage sensitive dye Di‐4‐ANEPPS were perfused into the isolated hearts by Langendorff method .LED source with the wave length of 532 nm was used to record APD80 and APD50 of the left and right ventricles .Experimental groups were divided into 3 groups by perfusion drugs dofetillide (30 nmol/L) ,dofetillide+ATX‐Ⅱ(1 nmol/L) ,and dofetillide +ATX‐Ⅱ +mexiletine (10μmol/L) .The subjects were intervened by the above drugs in order ,and they were self‐compared before dosing .After each drug administration ,the hearts were stimulated respectively with the BCL of 2 000 ms ,1 000 ms ,500 ms ,and 300 ms .Then we observed the changes of APD80 and APD50 in the left and right ventricles before and after the interventions .Results ① In the control group ,APD80 and APD50 of the right ventricle were longer than those of the left ventricle in response to different stimulation , and the differences increased with the decrease of stimulating frequency .② When BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles were prolonged respectively after administration of dofetillide , but the differences in APD80 and APD50 were insignificant between the left and right ventricles (P>0 .05) .ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency . ③ After administration of ATX‐Ⅱ , when BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles increased significantly compared with those in the control group and dofetillide intervention group (P<0 .05) .And the increase of APD in the left ventricle was greater than that of the right ventricle .ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency .④ After administration of mexiletine ,when BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles reduced significantly compared with those of the primary state (P<0 .05) .APD80 and APD50 of the left and right ventricles reduced significantly compared with those of the control group (P< 0 .05) and ATX‐Ⅱ group (P>0 .05) .The increase of ΔAPD80 of the two ventricles became milder when the stimulating frequency decreased . Conclusion ① IKr blocked by dofetillide did not affect the heterogeneity between the two ventricles , which showed reverse‐frequency dependence . ② In the context of blocking IKr , ATX‐Ⅱ increased the heterogeneity between the left and right ventricles and enhanced the reverse‐frequency dependence .In contrast ,mexiletine ,the blocker of INa‐L ,decreased the heterogeneity between the two ventricles and reverse‐frequency dependence .
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